Cachexia is a state with an unhealthy fatigue state, and is usually caused by anorexia from diseases and changes of endocrine system and immune system, resulting in wasting, loss of muscle and visceral proteins, finally in loss of body weight.
Cachexia is a syndrome used to be found in patients with chronic diseases or critical care. In particular to patients with stomach cancers or pancreas cancers among patients with cancers, and there are about 70% patients who will develop this syndrome. At the late stage of cancer, there are about 80% patients who will develop cachexia no matter what kind cancer they have. Cachexia is characterized by that there is no way to prevent or terminate loss of patients' body weight, even if you increase the food amount and enhance the nutrients intake for the patient. Hormonal appetite enhancer (such as megestrol, medroxyprogesterone acetate) is usually used in the treatment, however, someone has pointed out that it only results to a temporary increase of body weight (water and fat increase only), and there is no increase of body muscle, and there is no improvement on activity ability and physical activity. Contrarily, some drug side-effects are observed such as thrombus, edema, hemorrhage, hyperglycemia and hypertension and the like.
Catabolic wasting or cachexia is a syndrome characterized by spontaneously progressive wasting of fat and skeletal muscle, refractory body weight loss to increase nutrition import, increase of resting energy expenditure (REE), decrease of protein synthesis, change of carbohydrate metabolism (Cori cycle activity increase), over catabolism of ATP-ubiquitin dependent proteasomes pathway through protein solvent, and over catabolism of adipose tissue through adipose solvent (Body J J, Curr Opin Oncol 11: 255-60, 1999, Muscaritoli M, et al: Eur J Cancer 42: 31-41, 2006). In general, a patient will not be diagnosed cachexia until 5% or 5 pounds body weight loss at least. About half of patients with cancers experience certain level of catabolic wasting, and a higher attack rate is found in the cases with lung, pancreas and gastrointestinal malignant diseases (Dewys W D, et al: Am J Med 69: 491-7, 1980). The syndrome is found in patients with immunodeficiency diseases such as AIDS and patients with bacterial and parasitic diseases, rheumatoid arthritis, chronic diseases associated with bowel, liver, lung and heart. Cachexia also relates to anorexia, which may be a situation of aging or a result of body injury or burn. Cachexia syndromes reduce patients' functional ability and living quality, deteriorate potent situation, and reduce drug tolerance. The level of cachexia is inverse proportional to the survival time of patient, which usually means a poor prognosis. In recent years, diseases associated aging and disable has become a major issue in health care.
Anorexia (a medical term for appetite loss) is a deterioration of many malignant diseases, and is often found in patients with cancer, infectious diseases, chronic organ failure and trauma. Anorexia is a sever syndrome because it will cause a decrease calorie intake and dystrophy. Symptoms of anorexia include decrease of gestation and olfaction, early satiety, decrease of hunger sensation and even complete food aversion, and nausea and vomit may be found in some cases. The reasons of anorexia are not well known, and there are only limited options available for effective therapy. Some research has mentioned that a combination of hormone, social factor and psychological factor might be an important factor for the onset and progression of this syndrome.
It is not clarified a consistent relationship between cachexia onset and tumor size, disease stage, type and period of a malignant disease although cachexia is usually associated with cancer actually. The cancer cachexia usually associates with decrease of calorie intake, increase of resting energy expenditure, and metabolic change of protein, fat and carbohydrate. For example, some significant abnormality of carbohydrates includes: increase of total glucose conversion, increase of glyconeogenesis, glucose impaired tolerance and hyperglycemia. It is usually found an increase of fat solvent, increase conversion of free fatty acid and glycerol, hyperlipidemia, and decrease of lipoprotein lipase activity. It should be concerned that cachexia-associated body weight loss is not only caused by body fat storage loss but also related to body total protein mass loss and pervasive skeletal muscle wasting. An increase of protein conversion and impaired regulation of amino acid oxidation might be critical factors for this syndrome deterioration. Further, specific host influence factors produced corresponding to cancers, such as pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-1, interleukin-6 and γ-interferon), acute phase protein (e.g. C-reactive protein) and specific prostaglandin, are likely to associate with cancer cachexia.
In Chinese traditional herbal medicine, it is recommended that aged people take Poria galenical everyday, and it will help aged people to delay aging and have long life in addition to not easy to be sick.
The applicant of the present application in EP 1535619 A1 discloses a pharmaceutical composition for enhancing immunity in human body, which contains a lanostane compound as a potent component. This composition is able to enhance immunity and is useful in the prophylaxis and treatment of virus infections. On the other hand, the Poria extract and lanostanes purified therefrom show an inhibition effect on immunity, and are used in the prophylaxis and treatment of IgE-mediated allergies (asthma). This inhibition effect is disclosed in US2009 0318399 A1 and WO 2009/155/730 A1. These applications indicate that Poria extract and lanostanes are able to adjust immunity. The applicant of the present application in US 2009/0247496-A1 and WO 2009/124420 A1 discloses that Poria extract and lanostanes purified therefrom have an effect on human intestines and enhance the uptake of nutrients: absorption of glucose, amino acids, and vitamins (folic acid).
Therefore, Poria extract ingredient, particularly lanostane compounds, might help in improving and treating cachexia associated with nutrition and immunology. In this invention, whether or not the Poria extract ingredient and lanostane compounds have a treating effect on cachexia was evaluated by performing experiments with mice transplanted with human lung cancer cells, wherein the human lung cancer cell transplanted mice were observed as to whether they had normal appetite and had normal body weight without gradually losing their body weight in comparison with normal mice.